PHOSPHOLIPID/CALCIUM- DEPENDENT PROTEIN KINASE (PROTEIN KINASE C) SYSTEM" A MAJOR SITE OF BIOREGULATION J. F. KUO, MAMORU SHOJI, PEGGY R. GIRARD, GONZALO J. MAZZEI, R. SCOTT TURNER and HUAI-DE SU* Emory University School of Medicine, Atlanta, Georgia INTRODUCTION Phospholipid/Ca2+-dependent protein kinase (protein kinase C) (ATP: protein phosphotransferase, EC 2.7.I.37), discovered in 1979 by Nishizuka and associates (1), occurs widely in tissues and phyla of the animal kingdom (2, 3). The biological significance of this major, multifunctional protein phosphorylation system is supported by its involvement in membrane signal transductions, in which the enzyme is activated by diacylglycerol and Ca2+, the two intracellular mediators whose levels are augmented subsequent to phosphatidylinositol turnover elicited by activation of a wide variety of receptors (for reviews, see 4, 5). The presence of numerous but specific substrate proteins for the enzyme in discrete subcellular locations further underscores its pivotal role in cellular function and regulation (for general reviews, see 6-8). In this article, we present some of our recent studies on protein kinase C, emphasizing the regulatory aspects of the system. MATERIALS AND METHODS The materials and methods used in these studies have been described previously in the papers cited in this chapter. For unpublished and relevant studies, however, methods are described in the legends to the appropriate Figures. RESULTS AND DISCUSSION Substrate Specificity Determinants of Protein Kinase C as Probed with Synthetic Peptide Substrates and Inhibitors The substrate specificity has been studied for several classes of protein kinases. In addition to their specificity for different proteins as substrates, *On leave from Department of Pharmacognosy, Faculty of Pharmacy, Beijing Medical College,Beijing,China. 387